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目的评估新型β-链蛋白(β-catenin)结合药物SAHPA1在绝经后骨质疏松小鼠模型中的治疗效果。方法选取C57雌性小鼠作为实验对象。将实验动物分为3组,分别为假手术组、骨质疏松模型组(模型组)、骨质疏松模型治疗组(治疗组),每组5只小鼠。假手术组仅暴露卵巢后缝合切口;模型组和治疗组动物行双侧卵巢切除,建立去卵巢骨质疏松模型。治疗组在切除卵巢后即刻开始每日肌注β-catenin结合药物SAHPA1(10mg/kg),假手术组和模型组每日注射同剂量的生理盐水。8周后,利用骨组织切片H-E染色、micro-CT等方法观察小鼠股骨干骺端骨小梁形态并进行形态学计量分析,评估SAHPA1对去卵巢骨质疏松的治疗效果。结果与假手术组比较,模型组小鼠骨密度、骨小梁数量、骨小梁厚度均降低,差异有统计学意义(P<0.05)。经SAHPA1治疗后,小鼠骨密度和骨小梁数量增高(P<0.05),骨小梁厚度与模型组比较虽有一定提升但差异无统计学意义(P>0.05)。结论新型β-catenin结合药物SAHPA1对绝经后骨质疏松小鼠模型有一定治疗作用。
Objective To evaluate the therapeutic effect of a novel β-catenin-binding drug, SAHPA1, in a mouse model of postmenopausal osteoporosis. Methods C57 female mice were selected as experimental subjects. The experimental animals were divided into 3 groups: sham operation group, osteoporosis model group (model group) and osteoporosis model treatment group (treatment group), 5 mice in each group. The sham-operation group only exposed the posterior ovarian suture incision. The ovariectomized model group and the untreated group were ovariectomized and the ovariectomized osteoporosis model was established. The treatment group began intramuscular injection of β-catenin combined with SAHPA1 (10 mg / kg) immediately after ovariectomy. The rats in sham operation group and model group were injected daily with the same dose of saline. After 8 weeks, the morphology of the trabecular bone in the femoral metaphysis was observed by H-E staining and micro-CT, and morphometric analysis was performed to evaluate the therapeutic effect of SAHPA1 on ovariectomized osteoporosis. Results Compared with the sham operation group, the BMD, trabecular number and trabecular thickness in the model group decreased significantly (P <0.05). After SAHPA1 treatment, the BMD and trabecular number increased (P <0.05). There was no significant difference in the trabecular thickness compared with the model group (P> 0.05). Conclusion The new β-catenin binding agent SAHPA1 has a therapeutic effect on postmenopausal osteoporotic mouse model.